Hepatocyte-derived canine familiaris-microRNAs as serum biomarkers of hepatic steatosis or fibrosis as implicated in the pathogenesis of canine cholecystolithiasis.

BACKGROUND: Hepatic cholesterol accumulation in small breed dogs is a leading risk factor for hepatic fatty changes, gallbladder hypomotility, and cholelith development, which, if not discovered early, could lead to life-threatening choledocholithiasis and acute pancreatitis. OBJECTIVE: This study proposed to assess the use of hepatocyte-derived canine familiaris (cfa)-microRNAs (miRNA-122, -34a, and -21) as new diagnostic serum biomarkers of liver steatosis or fibrosis, for which both processes have been implicated in canine cholecystolithiasis. METHODS: Forty client-owned dogs diagnosed with cholecystolithiasis and hepatic steatosis (C+HS) or fibrosis (C+HF) based on ultrasonographic, biochemical, and histopathologic findings, and 20 healthy dogs used as controls were included in the study. Serum cfa-miRNA expression was determined using a real-time polymerase chain reaction assay. RESULTS: Serum cfa-miRNA-122 and -34a expression was significantly upregulated in the C+HS (P < .001) and C+HF (P < .01) groups compared with the control group and showed a positive correlation with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total cholesterol (TC), and triglycerides (TG) levels in the C+HS group. Cfa-miRNA-122 and -34a expression discriminated the diseased groups from the control group better than traditional serum-derived liver biomarkers, as evidenced by areas under the receiver operating characteristic (AUC-ROC) curve of 0.99 and 0.97 for cfa-miRNA-122 expression in the C+HS and C+HF groups, and 1.0 and 0.96 for cfa-miRNA-34a in the C+HS and C+HF groups, respectively. Cfa-miRNA-21 expression was upregulated only in the C+HF group compared with the C+HS (P < .01) and control (P < .001) groups and showed a positive correlation with serum ALT, AST, TBIL, ALP, and GGT and negative correlation with serum TC and TG levels. Cfa-miRNA-21 expression could also differentiate the C+HF group from the control and C+HS groups with a diagnostic performance superior to that of the conventional serum biochemical variables as evidenced by AUCs of 1.0 and 0.98, respectively. CONCLUSIONS: Serum cfa-miRNA-122, -34a, and -21 expression was significantly upregulated in dogs with cholecystolithiasis with hepatic steatosis or fibrosis compared with control dogs. These miRNAs could serve as novel biomarkers for hepatic steatosis or fibrosis, which have been implicated in the pathogenesis of cholecystolithiasis.

Preoperative diagnoses and identification rates of unexpected gallbladder cancer.

BACKGROUND: Unexpected gallbladder cancer (UGBC) is sometimes found in the resected gallbladder of patients during or after surgery. Some reports have indicated UGBC identification rates for all gallbladder surgeries, but scarce data are available for the UGBC identification rates for specific gallbladder diseases. The present study was performed to clarify UGBC rates and the factors suspicious for UGBC categorized according to preoperative diagnoses, in patients undergoing laparoscopic cholecystectomy (LSC). METHODS: We recorded data for all LSC surgeries performed in the Department of Surgery, Sada Hospital, Japan since 1991, and analyzed the 28-year data. We used the chi-square test and Kaplan-Meier analysis for this retrospective case-control study. RESULTS: The UGBC identification rate was 0.69% (63/9186 patients). The UGBC identification rates categorized according to the preoperative diagnoses were 1.3% (13/969) for acute cholecystitis, 2.4% (16/655) for benign tumor, 2.0% (28/1383) for chronic cholecystitis or cholecystitis, and 0.054% (3/5585) for cholecystolithiasis. The percentage of older patients (≥ 60 years) was significantly higher in UGBCs compared with cases finally diagnosed as benign in each group categorized according to the preoperative diagnoses (p≤0.0014), except for cholecystolithiasis. In cases pre-diagnosed as benign tumor, UGBCs were associated with higher rates of thickened gallbladder wall compared with benign tumor (69.2% vs. 27.9%, respectively; p = 0.0011). UGBCs pre-diagnosed as acute cholecystitis had higher T2-T4 rates (100% vs. 64.3%, respectively; p<0.05) and lower survival rates (p = 0.0149) than UGBCs pre-diagnosed with chronic cholecystitis. CONCLUSIONS: UGBC identification rates depend on the preoperative diagnosis and range from 0.054% to 2.4%. Older age (≥ 60 years) could be related to UGBC, and a pre-diagnosis of acute cholecystitis might indicate more advanced cancer compared with a pre-diagnosis of chronic cholecystitis.

A Resected Gallbladder Carcinoma Coexisting With Adenomyomatosis Involving Varied Degrees of Intraepithelial Dysplasia: A Case Report and Literature Review.

A 59-year-old asymptomatic man underwent ultrasonography, which revealed gallstones and thickened gallbladder wall. Abdominal computed tomography (CT) showed a slightly swollen bilocular gallbladder and a soft tissue mass in the fundus site. Segmental adenomyomatosis (ADM) was suspected because numerous fundic cystic lesions were seen on magnetic resonance imaging. Endoscopic ultrasonography revealed numerous Rokitansky-Aschoff sinuses (RAS) and a papillary soft tissue shadow surrounded with irregular and remarkably thickened fundic gallbladder wall. Fluoro-2-deoxy-D-glucose-positron emission tomography/CT demonstrated slightly increased fluoro-2-deoxy-D-glucose uptake in the corresponding lesion. Surgery was performed under a diagnosis of gallbladder carcinoma (GBC) with concomitant ADM, and histopathology revealed a 30-mm papillotubular adenocarcinoma extending from the gallbladder body to fundus with invasion into the subserosa. Numerous RAS were present throughout the gallbladder showing various degrees of dysplasia. Ki67 and p53-labeling index (LI) was significantly higher in the dysplastic epithelium compared with normal fundic epithelium. p53-LI was also markedly increased (72.1%) in tissue in front of tumor invasion. Interestingly, these hyperproliferation indicators were extremely high (Ki67-LI: 28.8%; p53-LI: 91.9%) in RAS with low-grade dysplasia even in the gallbladder neck. Although, generally, tumors do not develop in the gallbladder neck with segmental ADM, our results suggest that a gallbladder with ADM has potential for carcinogenesis regardless of location, with segmental ADM. On the basis of histopathology, our patient was diagnosed with GBC arising from RAS with multicentric and multistep growth. A relationship between GBC and ADM, especially segmental ADM, has been suggested but remains controversial. Our experience is very suggestive of carcinogenesis developing from ADM.

[Bouveret's syndrome - a rare complication in connection with cholecystolithiasis and a variant of gallstone ileus].

Bouveret's syndrome is a very rare complication to cholecystolithiasis resulting in gallstone ileus. It is caused by ectopic gallstones in the duodenum due to a bilioenteric fistula. Symptoms may include vomiting and upper abdominal pains. The condition is associated with high mortality, making it important to recognize. The treatment includes surgical removal of the gallstone. However, the optimal therapeutic approach has still not been found. In this case report a 59-year-old female with Bouveret's syndrome is presented.

[Clinical and laboratory diagnosis of an acute biliary pancreatitis].

In 126 patients, suffering an acute biliary pancreatitis (ABP), clinical examination was conducted. In 65 patients (1-st group) the isolated cholecystolithiasis was noted; in 35 (2-nd group)--cholelithiasis, which did not cause obturation of common biliary duct; in 26 (3-rd group)--cholelithiasis, which caused the biliary ways obturation (including calculi, which were incorporated into the duodenal papilla magna ostium). Clinical course of an ABP have differed depending on localization of calculi of extrahepatic biliary ducts. In patients, suffering ABP, a biochemical signs of hepatocytes functional disorders were observed, impacting the need for hepatoprotector preparations inclusion into complex of perioperative conservative therapy. Determination of activity of pancreatic α-amylase in the blood serum and conduction of the ACTIM Pancreatitis test con- stitute the most sensitive and specific methods of the ABP biochemical diagnosis.

[Application of cholecystectomy in surgical treatment of chronic calculous cholecystitis].

Morphological peculiarities of the excised gallbladder were studied in 106 patients, ageing from 24 to 74 yrs, who were treated for chronic calculous cholecystitis. Interrelationship between results of ultrasound investigation preoperatively and morphologic forms was established, what have permitted to select the operative intervention procedure, including conduction of organ preserving operations--cholecystolithotomy.

[Cholecystolithiasis as a cause of local hepatitis].

In an acute inflammation of gallbladder inflammatory process spreads on surrounding tissues, including hepatic tissue, what causes the regional hepatitis occurrence. In some patients, suffering calculous cholecystitis on background of transition of inflammatory process from gallbladder to hepatic tissue likewise a regional hepatitis, hyperbilirubinemia, the skin yellowness are revealed, what simulates choledocholithiasis and obturation jaundice.

Abdominal regional fat distribution on MRI correlates with cholecystolithiasis.

AIMS: To determine whether abdominal regional fat distribution pattern on MRI is correlated with cholecystolithiasis. METHODS: Magnetic resonance imaging (MRI) of 163 patients with cholecystolithiasis and 163 non-cholecystolithiasis control subjects admitted to our institution between March 2011 and September 2013 were included in this cross-sectional evaluation. There were 98 women and 65 men in cholecystolithiasis group with an average age of 57±16 years (range 25-86 years). There were 87 women and 76 men in the control group with an average age of 41±16 years (range 14-77 years). Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and total abdominal adipose tissue (TAT) of all the subjects at navel level were measured on abdominal MRI. According to the visceral adipose area (cut-off point VAT = 100 cm2), study subjects were divided into 1) increased accumulation of intra-abdominal fat and 2) normal distribution of intra-abdominal fat. Logistic regression was used to assess the association of fat with the presence of cholecystolithiasis, adjusted for age and sex. RESULTS: The incidence of increased intra-abdominal fat accumulation in the cholecystolithiasis group was significantly higher than that of the control group (P = 0.000). After adjusting for age and sex, cholecystolithiasis was associated with a one standard deviation increment in the waist circumference (WC) (OR = 1.44; 95%CI: 1.01,1.93; p = 0.00), VAT (OR = 4.26; 95%CI: 1.85,5.29; p = 0.00), VAT/SAT (OR = 8.66; 95%CI: 1.60,12.63; p = 0.00), and VAT/TAT (OR = 6.73; 95%CI: 4.24,12.18; p = 0.00), but not with fat content in the abdominal subcutaneous fat (p = 0.19). CONCLUSIONS: The visceral adipose tissue and distribution proportion of abdominal adipose tissue are correlates of cholecystolithiasis.

Biliary dyskinesia and symptomatic gallstone disease in children: two sides of the same coin?

BACKGROUND: Despite lack of consensus criteria, biliary dyskinesia (BD) is an increasingly accepted pediatric diagnosis. AIMS: We compared patient characteristics, outcomes, and resource utilization (before and after surgery) between children with BD and symptomatic cholecystolithiasis (LITH). METHODS: Data from the electronic medical record were abstracted for children diagnosed with BD or LITH between December 1, 2002, and November 30, 2012, at Children's Hospital of Pittsburgh. RESULTS: Four hundred and ten patients were identified (BD: 213 patients, LITH: 197 patients). Patients with BD had significantly lower BMI, longer symptom duration, more dyspeptic symptoms, and were more likely to present with other symptoms. Forty-one patients (13.8%) with BD underwent cholecystectomy despite a normal gallbladder ejection fraction (GB-EF). In 32 of these, sincalide triggered pain compared to 75 of the 155 patients with low GB-EF. After surgery, patients with BD more commonly visited gastroenterology clinics and had more GI-related hospitalizations, while emergency room visits decreased in both groups. Only the nature of biliary disease independently predicted continuing pain after surgery, which in turn was the best predictor for higher resource utilization after cholecystectomy. CONCLUSIONS: A large percentage of children with BD did not meet the adult diagnostic standards. Compared to those with LITH, children with BD have more widespread symptoms and continue to use more clinical resources after surgery. These findings suggest that despite its benign prognosis, BD is increasingly treated like other potentially acute gallbladder diseases, although it has the typical phenotype of FGIDs and should be treated using approaches used in such disorders.

[Combined laparoscopic operations in patients with acute appendicitis and biliary calculous disease].

The experience of surgical treatment was summarized in patients, suffering an acute appendicitis, in whom simultaneously a biliary calculous disease was revealed. The procedure and technical aspects of performance of simultant laparoscoplic operation were depicted, the indications and contraindications for simultant operation conduction were determined, a consequence of the operative stages performance was determined. The main advantages of simultant laparoscopic operations were proved and the results of treatment analyzed.

A newly developed oval-shaped port device (E•Z ACCESS Oval type) for use in reduced port surgery: initial clinical experiences with cholecystectomy.

We recently developed an oval-shaped E•Z Access device designed exclusively for use with the LAP PROTECTOR™ Oval type device (Hakko Co. Ltd., Tokyo, Japan). The transverse abdominal opening diameter made by round-shaped (Alexis® Wound Retractor, Applied Medical, Rancho Santa Margarita, CA; and LAP PROTECTOR™ Round type) and oval-shaped (LAP PROTECTOR™ Oval type) wound retractors was measured and compared in 5 patients with cholecystolithiasis. Each device was placed through a single 25-mm longitudinal umbilical incision, and the length of trocar separation was compared. LESS cholecystectomy was then performed using the oval-shaped E•Z ACCESS/LAP PROTECTOR™. The transverse abdominal opening diameter was maximized with the LAP PROTECTOR™ Oval type device. The average distance between the working-ports for the glove method, round-shaped, and oval-shaped E•Z ACCESS/LAP PROTECTOR™ devices in the 25-mm umbilical incisions were 20 ± 0.8 mm, 24 ± 1.5 mm, and 35 ± 0.8 mm, respectively. Wider trocar separation was achieved using the oval-shaped device, making the surgical procedures easier to perform. No perioperative port-related or surgical complications were observed. LESS cholecystectomy using the E•Z ACCESS Oval type device was found to be technically feasible. The Oval type device appears to allow for wider trocar separation, thereby reducing stress on the surgeon, ensuring patient safety, and providing cosmetic benefits.

Single-incision laparoscopic cholecystectomy for cholecystolithiasis coinciding with cavernous transformation of the portal vein: report of a case.

BACKGROUND: Cavernous transformation of the portal vein (CTPV) is a rare vascular deformity. It is thought to be secondary to extra-hepatic portal vein obstruction, with formation of serpiginous collateral vessels around the extra-hepatic bile duct, and even the gallbladder. Surgery is difficult because the vessels have irregular courses, are somewhat fragile and bleed easily. Single-incision laparoscopic cholecystectomy, an emerging procedure for symptomatic cholecystolithiasis, has limitations especially in anatomically complex cases. CASE PRESENTATION: We describe a 44-year-old woman with symptomatic cholecystolithiasis. Computed tomography revealed a series of tortuous collateral veins at the liver hilum, with the extra-hepatic portal vein occluded at the level of the spleno-portal junction. However, the distended vessels were not particularly close to the cystic duct. We performed single-incision laparoscopic surgery (SILS) for cholecystectomy via a trans-umbilical incision. By pulling the cystic duct out along with neighboring cavernous vessels, we were able to secure detachment of the cystic duct from Calot's triangle and ligation of the cystic artery. Total operating time was 132 minutes and blood loss was 370 grams. The patient was discharged on postoperative day 2 with no perfusion abnormalities in the liver. CONCLUSION: We must pay meticulous attention to the area of Calot's triangle when performing SILS cholecystectomy with CTPV. SILS cholecystectomy might be an option in highly experienced facilities.

Tiny cystine stones in the gallbladder of a patient with cholecystolithiasis complicating acute cholecystitis: a case report.

Cystine stones, the main component of which is cystine, are very common urinary calculi, but are rare in the gall bladder. In animals, there has been only one report of cystine gallstones in tree shrews, and to our knowledge, this is the first report of cystine gallstones in humans.

The correlation between ultrasonography and histology in the search for gallstones.

INTRODUCTION: The majority of published data on the sensitivity and specificity of ultrasound in the diagnosis of gallbladder pathology was conducted over 30 years ago and, since the 1990s, ultrasound imaging has been the accepted gold standard. The quality and resolution of ultrasonography has improved significantly since then and we have, therefore, set out to assess whether the progression in technology has translated into improved diagnostic accuracy. PATIENTS AND METHODS: In the period December 2005 to December 2008, a total of 2100 patients underwent laparoscopic cholecystectomy for symptoms related to gallbladder disease. All patients underwent ultrasound examination prior to their surgery and histopathological analysis of their gallbladder postoperatively. We undertook a retrospective analysis of these patients comparing their pre-operative ultrasound scan and their histopathology report for the presence or absence of gallstones. Ultrasound scans were performed by a combination of radiologists and ultrasonographers. RESULTS: The study identified a sensitivity of 0.85 and a specificity of 1 for ultrasound in the identification of gallstones. We found a sensitivity of 0.84 and 0.83 for the radiologists and ultrasonographers, respectively. CONCLUSIONS: This study suggests that, despite an evolution in the resolution of ultrasound imaging, there has not been a corresponding improvement in sensitivity. There is a false positive rate of 16% which remains unchanged since the early 1990s.

[Psychosomatic aspects of pathology of biliary passages].

The work was designed to study psychological features of patients with hypomotor dysfunction of biliary passages, chronic non-calculous cholecystitis with and without opistorchosis and cholelithiasis before and after cholecystectomy. A total of 343 patients were examined between 1997 and 2007. The control group comprised 100 age- and sex-matched healthy subjects. All patients signed the informed consent. Significance of the difference between absolute and relative parameters was estimated using Student's t-test at three significance levels (0.05, 0.001, 0.001---??). There were no differences between psychological status of patients with biliary duct pathology, but they were significantly different from controls as regards this variable. Patients with different forms of biliary duct pathology showed unidirectional changes of psychological symptoms that deteriorated with severity of the main disease. The psychological portrait of the patients suggested emotionally labile, hypochondriac, irritable, self-confident, highly anxious and neurotic personality type.

[The role of laparoscopy in the surgical treatment of scleroatrophic cholecystitis]. / Locul laparoscopiei in chirurgia colecistitei scleroatrofice litiazice.

Atrophic cholecystitis is a chronic inflammatory complication of biliary lithiasis which occurs after many years of evolution and causes many problems in the surgical therapy. Authors analyze a 39 patients cohort and present the difficulties encountered during the treatment, especially in laparoscopic approach. These particular difficulties lead to a increase in conversion rate, 11.1%, much higher that in average laparoscopic cholecystectomy. The conclusion of this study is that this disease still remains a challenge for surgeons, especially in laparoscopic approach, and the conversion an elegant way to avoid severe intraoperative accidents.

Clinico-pathological spectrum of gallbladder disease in children.

AIM: Because of wide variation in clinico-pathological spectrum of gallbladder disease in children the world over, the data of gallbladder disease from this stone belt of India were analysed. METHODS: Children who underwent cholecystectomy over a period of 8 years January 2002-December 2009 were reviewed. RESULTS: Out of 7076 cholecystectomies, 56 (0.79%) were in children. Thirty-nine (69.6%) children were 11-16 years of age. Thirty-seven (66.07%) children were girls and nineteen (33.9%) were boys. In 12 (21.4%) children, cholecystitis was acalculus. Five (8.9%) children had associated haemolytic disease and 4 (7.1%) children had congenital anomaly in the form of choledochal cyst. Ultrasound findings were available in 44 cases and showed cholelithiasis in 36 cases. Twenty-two (39.3%) children had mixed cholelithiasis, 8 (14.2%) pigment cholelithiasis, 10 (17.8%) combined cholelithiasis and 4 (7.1%) patients had small concretions. Microscopically, changes of chronic cholecystitis were seen in 98.2% while 1.7% showed acute on chronic cholecystitis. There was single unusual case of cysticercus in the wall of the gallbladder. CONCLUSIONS: The frequency of gallstone disease is 0.79%. Nonhaemolytic type of cholelithiasis is more common than haemolytic type in this region. Presence of cysticercus in the gallbladder wall in one case was an unexpected finding.

Long-term outcome of endoscopic papillotomy for choledocholithiasis with cholecystolithiasis.

AIM: To assess long-term outcome of endoscopic papillotomy alone without subsequent cholecystectomy in patients with choledocholithiasis and cholecystolithiasis. METHODS: Retrospective review of clinical records of patients treated for choledocholithiasis and cholecystolithiasis from 1976 to 2006. Of 564 patients subjected to endoscopic papillotomy and endoscopic stone extraction, 522 patients (279 men, 243 women; mean age 66.2 years) were followed up and predisposing risk factors for late complications were analyzed. RESULTS: The mean duration of follow up was 5.6 years. Cholecystitis and recurrent choledocholithiasis occurred in 39 (7.5%) and 60 (11.5%) patients, respectively. Cholecystitis, including one severe case, resolved with conservative treatment. Recurrent choledocholithiasis was successfully treated endoscopically except in one case. Pneumobilia was found to be a significant risk factor for cholecystitis (P = 0.019) and recurrent choledocholithiasis (P = 0.013). Biliary tract cancer occurred in 16 patients; gallbladder cancer in 13 and bile duct cancer in three. Gallbladder cancer developed within 2 years after endoscopic papillotomy in seven of the 13 patients (53.8%). CONCLUSION: Pneumobilia was the only significant risk factor for cholecystitis and recurrent choledocholithiasis in our study population. As for the long-term outcome, it was unclear whether endoscopic papillotomy contributed to the occurrence of biliary tract cancer.